title: Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides.
abstract: Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin and CCK and, hence, their effect on insulin secretion are modest in comparison with the effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1). Consequently, the interest of CCK and gastrin in incretin research has for decades been limited. A few years ago, however, it was suggested that gastrin together with epidermal growth factor or later GLP-1 might stimulate beta cell growth and secretion. Recent studies have shown that the combination of gastrin and GLP-1 actually restores normoglycaemia in diabetic mice. Therefore, a short review of the incretin system in a broader functional context that includes gastrin and CCK peptides may be timely.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. jens.f.rehfeld@rh.regionh.dk
authors.forename: J F
authors.initials: JF
authors.lastname: Rehfeld
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism
chemical_list: D005755:Gastrins; D054795:Incretins; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin